The placenta contains a large variety of metabolizing enzymes, among them UDP-glucuronosyltransferase (UGT). Several UGT2B isozymes have so far been detected in human placenta, but little is known on placental expression of UGT1A isozymes. The antiepileptic drug lamotrigine (LTG) is a UGT1A4-substrate, and its serum concentration falls by over 50% during pregnancy, leading to impaired seizure cont

Purpose: To study the interaction between lamotrigine (LTG) and hormonal contraception. Methods: LTG serum concentrations of female patients using either no hormonal contraception (n = 18), an ethinyl estradiol (EE)-containing (n = 11), or a progestogen (PG)-only-containing compound (n = 16) were analyzed. Patients were recruited prospectively, and blood samples were drawn during drug fasting and

After common belief the impairment of nerve conduction seen with multiple sclerosis has to do with uncovering of internodal potassium channels. Therefore, suitable potassium channel blockers like 5-methoxypsoralen can alleviate functional deficits due to multiple sclerosis. This has been demonstrated by single tests under well-defined laboratory conditions and by further clinical single trials. Wi

The effects of myoglobin on renal microcirculation were studied in anesthetized rats subjected to hemorrhagic hypotension. Capillary flow distribution was determined by allowing two dyes to circulate for 3 and 1 min, respectively, freezing the left kidney and quantifying the dye distribution in histological sections by analyzing the distances of regularly spaced test points to the next dye-labeled

Depression is common during pregnancy, and a considerable proportion of pregnant women take antidepressants. Modern antidepressants (e.g. SSRIs) are fairly safe to use during pregnancy. Several physiological changes occur in the pregnant state, possibly affecting the pharmacokinetics of many drugs. Metabolism via CYP enzymes are important for the elimination of antidepressants. This metabolism mayDepression is common during pregnancy, and a considerable proportion of pregnant women take antidepressants. Modern antidepressants (e.g. SSRIs) are fairly safe to use during pregnancy. Several physiological changes occur in the pregnant state, possibly affecting the pharmacokinetics of many drugs. Metabolism via CYP enzymes are important for the elimination of antidepressants. This metabolism may

Purpose: To investigate the change in zonisamide (ZNS) serum concentration and its consequences in pregnant women with epilepsy. Methods: Six hospitals in Norway and Denmark screened their records for women who had been using ZNS during pregnancy. Absolute serum concentrations as well as concentration/dose (CD)-ratios were compared to non-pregnant values. Descriptive data on seizure control and ob

Background and objective: Laboratories sometimes use different reference ranges for the same antiepileptic drug (AED), particularly for new and poorly investigated drugs. This may contribute to misunderstandings, concerns or inappropriate dose changes, which in turn may affect therapeutic effect, drug safety or treatment adherence. Therefore, the Norwegian Association of Clinical Pharmacology wish

Purpose High initial serum concentrations increase the risk of cutaneous adverse reactions. Genetic variants of the main metabolizing isoenzyme, uridine diphosphate glucuronosyltransferase (UGT) 1A4 influence the elimination of lamotrigine (LTG). Our aim was to investigate the potential association between the two best studied variants, *2 (P24T) and *3 (L48V), and the occurrence non-bullous skin

Background Eslicarbazepine acetate (ESL) is a new antiepileptic drug (AED), still insufficiently studied regarding pharmacokinetic variability, efficacy and tolerability. The purpose of this study was to evaluate therapeutic drug monitoring (TDM) data in Norway and relate pharmacokinetic variability to clinical efficacy and tolerability in a long-term clinical setting in patients with refractory e

Lamotrigine (LTG) is an antiepileptic drug that is metabolized via glucuronidation. Since the glucuronidizing enzyme is inducible by estrogens, LTG serum concentrations may fall by 50–60% when combined with hormonal contraceptives that contain ethinyl estradiol (EE). Little is known about a possible interaction between estrogens used for hormone replacement therapy (HRT) and LTG, and the few avail

Background: Eslicarbazepine acetate (ESL) is a new anti-epileptic drug (AED) chemically related to oxcarbazepine (OXC) and carbamazepine (CBZ) and is increasingly used in clinical practice. The purpose of the study was to investigate 2-way pharmacokinetic interactions between ESL and other AEDs as compared to OXC and CBZ. Methods: Anonymous data regarding age, gender, use of AEDs, daily doses and

The gene encoding uridine diphosphate glucuronosyltransferase (UGT) 1A4 shows considerable polymorphism. Several common drugs are metabolised by UGT1A4, among them lamotrigine (LTG). Experimental and clinical studies suggest that certain variants of UGT1A4 are associated with altered enzyme activity. However, results are conflicting. This clinical study aimed to investigate the frequencies of two

The aim was to assess the clinical relevance of antiepileptic drug (AED) nonadherence by means of therapeutic drug concentration monitoring (TDM). Two hundred eighty-two consecutive patients with epilepsy acutely admitted to hospital for seizures were included. Nonadherence was defined as having a serum concentration/dose ratio at admission of

Caffeine acts as a central nervous stimulant by blocking A1 and A2A adenosine receptors. Its effect on seizures is complex. Animal studies and case reports indicate that acute caffeine exposure may induce seizures, whereas chronic exposure might have an opposite effect. Patients acutely hospitalized for seizures (n=174) were asked for their consumption of caffeinated beverages 24. h prior to admis

Purpose: To investigate the physiological mechanisms behind the pronounced decline of lamotrigine (LTG) serum concentrations during pregnancy. Methods: Serum and urine concentrations of LTG and its main metabolite, LTG-N2-glucuronide (LTG-GLUC), were measured monthly in 21 pregnancies of 19 women using LTG. Simultaneously, a panel of biochemical variables was monitored to evaluate liver and kidney

Objective: To investigate the impact of age and co-treatment with other drugs on the serum concentrations of lamotrigine in children and adolescents. Methods: A review of routine serum concentration measurements of lamotrigine performed in our laboratory yielded a total of 744 serum samples from 296 subjects (110 males, 186 females, age: 2-19 years) suitable for statistical analysis. The primary o

OBJECTIVES: To measure the serum concentrations of lamotrigine throughout a complete menstrual cycle. METHODS: Serum concentrations of lamotrigine, estradiol, and progestogen throughout a menstrual cycle were measured in 2 young women not using hormonal contraception. RESULTS AND CONCLUSIONS: The physiological hormonal fluctuations during an ovulatory cycle were not associated with clinically rele

Background. In some situations, and particularly when intoxications are suspected, it would be advantageous if medicines and drugs of abuse could be swiftly detected in serum or urine. Material and methods. The Department of Clinical Pharmacology at St. Olav University Hospital has since 2004 been developing a comprehensive toxicology service (at all hours 7-days/week) for immediate quantitative a